Rv3466 Still unknown · low auto-curated
H37Rv Rv3466 · MTBC0 - ·
222 aa · 3883525–3884193 (+) ·
RefSeq NP_217983.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Conserved hypothetical protein; DUF domain(s) DUF222. Function unknown. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WKY1
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Uncharacterized protein Rv3466 |
UniProt still lists this protein as Uncharacterized protein Rv3466; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
V Defense mechanisms
|
|---|---|
| eggNOG description | Domain of unknown function (DUF222) |
| Orthologous group | COG1403 |
| Gene Ontology (10) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0030312, GO:0040007, GO:0044464, GO:0071944
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.588 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 6 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
DUF222 | PF02720.23 | 6.4e-22 | 38–138 | Domain of unknown function (DUF222) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlC (dTDP-4-dehydrorhamnose 3,5-epimerase), medium confidence from genomic context alone (score 576 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3467 hyp |
hypothetical protein | 793 | 793 ctx | neighborhood:774 |
Rv1588c hyp |
hypothetical protein | 762 | 761 | coexpression:761 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 576 | 576 ctx | neighborhood:571 |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 573 | 573 ctx | neighborhood:571 |
Rv3463 hyp |
hypothetical protein | 442 | 441 ctx | neighborhood:433 |
Rv2100 hyp |
hypothetical protein | 816 | 98 | textmining:805 |
Rv0336 hyp |
hypothetical protein | 818 | 93 | textmining:808 |
Rv0515 hyp |
hypothetical protein | 704 | 89 | textmining:689 |
Rv1378c hyp |
hypothetical protein | 447 | 70 | textmining:430 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): DUF222 PF02720.23 (E=6e-22)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_217983.1)
- Domains: Pfam-A via hmmscan --cut_ga — DUF222 (PF02720.23)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG1403 - Curated reference: UniProt P9WKY1 (SwissProt, reviewed; Inferred from homology)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Model confidence: ESMFold per-residue pLDDT (mean 89.2, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
9 functional partner(s); context anchor
rmlC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3466| MGSGSRERIVEVFDALDAELDRLDEVSFEVLTTPERLRSLERLECLVRRLPAVGHALINQLDAQASEEELGGTLCCALANRLRITKPDAARRIADAADLGPRRALTGEPLAPQLTATATAQRQGLIGEAHVKVIRALFRPPARRGGCVHPPGRRSRPGRQSRSISSRRAGPLRPAGHGLATPRRRPHRHRTRPQTRHHPEQPAIRRHVTAKWLPDPPSAGHL